Months Of Ketogenic Diet Treatment Research Articles

Ketogenic Diet: Parental Experiences and Expectations.

The ketogenic diet may be difficult for some patients and their families to implement and can impact physical, emotional, and social well-being. Through principles of fundamental qualitative description, we completed an exploratory study on parents' experiences and expectations on the use and efficacy of the ketogenic diet for children with medically refractory epilepsy. Seventeen parents (10 mothers and 7 fathers) of 12 children with epilepsy participated. At the time of the interview, parents had experienced an average of 25 months of ketogenic diet treatment for their child (range 2 months to 98 months). Half of the caregivers learned about the ketogenic diet from their neurologist, whereas the remainder had heard about it from another source (ie, the internet). Most caregivers' (n = 13) diet expectations were related to seizure control. However, child development (n = 5) and quality of life (n = 5) were also crucial to some. Physical impacts of the diet were most commonly gastrointestinal for children (n = 9). Social and emotional effects were noted in some older children with typical development. Most caregivers described negative impacts on finances (n = 15), relationships (n = 14), and emotional well-being (ie, stress) (n = 12). Caregivers benefited from the ketogenic diet team's regular communication, close follow-up, and family-centered care. Despite the impacts that the ketogenic diet may have on caregivers' emotional and social well-being, the positive impacts of the diet were felt to outweigh any perceived risks. Effects (both positive and negative) on quality of life and child development (eg, social, emotional, cognitive) are essential for caregivers and require additional investigation.

Gut flora and metabolism are altered in epilepsy and partially restored after ketogenic diets

ObjectiveThe aim of this study was to investigate the composition of the intestinal microbiota and its association with fecal short chain fatty acids (SCFAs) in children with drug refractory epilepsy (DRE) before and after treatment with a ketogenic diet (KD). MethodsHerein, we conducted a cross-sectional study of 12 children with DRE and 12 matched healthy controls to compare the changes in fecal microbiomes and SCFAs. Disease cohort also underwent analysis before and after 6 months of KD treatment. ResultsA higher microbial alpha diversity and a significant increase in Actinobacteria at the phylum level and Enterococcus, Anaerostipes, Bifidobacterium, Bacteroides, and Blautia at the genus level were observed in the children with DRE. The abundance of the eight epileptic-associated genera was reversed after six months of KD treatment with decreases in Bifidobacterium, Akkermansia, Enterococcaceae and Actinomyces and increases in Subdoligranulum, Dialister, Alloprevotella (p < 0.05). In particular, we identified some taxa that were more prevalent in patients with an inadequate response to KD than in those with an adequate response. Further, a significant correlation was observed between the change in the microbiome genera after KD treatment. The SCFA content in the fecal after 6 months of KD treatment increased and was highly correlated with the gut bacteria. SignificancesDysbiosis of the microbiome could be involved in the pathogenesis of DRE in children, which can be relieved by a KD to a large extent. Gut microbiota and microbial metabolism could contribute to the antiseizure effect of KD.

The efficacy and safety of a ketogenic diet for children with refractory epilepsy in China: a retrospective single-center cohort study.

BackgroundThe ketogenic diet (KD) has been implemented in many different counties. However, in China, study concerning the efficacy of the KD is still at an early-stage of evaluation. Furthermore, the KD is thought to be incompatible with Chinese children because of its lack of palatability, especially for the Asian population. In addition, its substantial antiepileptic effect remains to be confirmed.MethodsTo evaluate the efficacy and safety of the KD treatment of refractory childhood epilepsy in China, we prospectively enrolled 147 children with refractory epilepsy for KD treatment in Guangdong 999 Brain Hospital and followed up the children for 6 months. Outcome was measured by seizure frequencies before and after the KD diet and adverse effects. We also evaluated influences of different variables (starting age, duration of epilepsy, and others) on the outcome.ResultsWe found after 1 month, 3 months, and 6 months of KD treatment, 28.0%, 55%, and 67.9% of the subjects remained on diet with a >50% seizure reduction and seizure-free rates of 6.5%, 13.2%, and 23.3%, respectively. Gender, starting age, duration, etiology, classification, and seizure type of epilepsy showed no significant influence on efficacy. Anorexia, diarrhea, and gravel were the main side-effects of the KD treatment.ConclusionsIn conclusion, the KD is a safe and efficacious method for childhood refractory epilepsy treatment.

Effect of Ketogenic Diet on Motor Functions and Daily Living Activities of Children With Multidrug-Resistant Epilepsy: A Prospective Study.

To investigate the effect of ketogenic diet on motor function and daily living activities in children with epilepsy. A total of 62 children (median age 5.0 years) were enrolled. Motor function was assessed using the Gross Motor Function Measure (GMFM), and daily living activities and cognitive functions were assessed using the Functional Independence Measure (WeeFIM) before treatment and 3, 6, and 12 months after ketogenic diet treatment. Significant improvement in total GMFM and WeeFIM scores ( P < .001) were found during the 12 months of ketogenic diet treatment. There was a positive correlation between total GMFM scores and WeeFIM scores at baseline (r= 0.792, P = .0001), and at 3 (r= 0.780, P = .0001), 6 (r= 0.744, P = .0001), and 12 months (r= 0.692, P = .0001) of treatment. Both the responder (50 patients, 80.7%) and nonresponder (12 patients, 19.3%) patient groups showed significantly higher GMFM and WeeFIM scores at 12 months of treatment compared to baseline values. A ≥50% reduction in seizure frequency was observed in 77.4%, 72.6%, and 80.7% of the patients after 3, 6, and 12 months of treatment, respectively. Ketogenic diet treatment improves motor functions and daily living activities in children with epilepsy during the 12 months of treatment.

Efficacy and retention rate of ketogenic-diet treatment in infantile spasm

Objective To explore the effectiveness and compliance of ketogenic-diet(KD) treatment for infantile spasm(IS). Methods Ninety-eight IS patients who were treated with KD in Wuhan Children′s Hospital from March 2009 to June 2015 were analyzed by using retrospective case-control study, the patients were divided into 4 groups: newly diagnosed IS patients group(group A, including 24 patients), one antiepileptic drug(AEDs) failure IS patients (group B, including 28 patients), two and more AEDs failure IS patients(group C, including 29 patients), and two or more AEDs combined with ACTH failure IS patients( group D, including 17 patients). The spasm-free and retention rates after 3, 6 and 12 months KD treatment were compared among these groups. Results Overall retention rate was 80.6%(79/98 cases), 69.4%(68/98 cases), and 42.9%(42/98 cases)at 3, 6, 12 months, respectively.The 3-month retention rate in group A, B, C and D was 83.3%(20/24 cases), 78.6%(22/28 cases), 82.7%(24/29 cases) and 76.4%(13/ 17 cases) respectively, and there was no significant difference among these groups(P>0.05). The 6-month retention rates in each group was 75.0%(18/24 cases), 67.9%(19/28 cases), 68.8%(20/29 cases) and 65.0%(11/17 cases) in sequence, and there was also no significant difference among these groups(P>0.05). The 12-month retention rate was 54.2%(13/24 cases), 21.4%(6/28 cases), 48.3%(14/29 cases) and 52.9%(9/17 cases) in group A, B, C and D in sequence, the 12-month retention rate of group B was significantly lower than that of other 3 groups, and the differences were statistically significant( χ2= 5.973, 4.508, 4.727, all P 0.05). The spasm-free rate at 3, 6, 12 months of KD treatment was 19.4%(19/98 cases), 20.4%(20/98 cases), 30.6%(30/98 cases). The 3-month spasm-free rate in A, B, C, D groups were as follow: 41.7%(10/24 cases), 14.3%(4/28 cases), 10.3%(3/29 cases), 11.8%(2/17 cases), respectively.The 3-month spasm-free rate in group A was significantly higher than that of other 3 groups, and the differences were statistically significant (χ2=10.238, 9.219, 6.697, all P 0.05). The 6-month spasm-free rates were 41.7% (10/24 cases), 14.3%(4/28 cases), 13.8%(4/29 cases), and 11.8%(2/17 cases) in group A, B, C and D in order, and the spasm-free rate in group A was significantly higher than that of other 3 groups, and the differences were statistically significant(χ2=4.924, 5.249, 4.298, all P 0.05). The 12-month spasm-free rates were 54.2% (13/24 cases), 21.4%(6/28 cases), 24.1%(7/29 cases), and 23.5%(4/17 cases) in group A, B, C and D, and the spasm-free rate in group A was significantly higher than that in other 3 groups, and the differences were statistically significant(χ2=8.354, 7.923, 4.364, all P 0.05). Conclusions The spasm-free rate of KD therapy for newly-diagnosed IS is higher than that of IS patients whose drug-therapy failed.KD therapy may be the top priority for IS patients and part of those patients whose drug-therapy failed can still get seizure-free with KD diet. Key words: Infantile spasm; Ketogenic-diet; Rate of spasm-free; Retention rate

The Effect of Ketogenic Diet on Serum Selenium Levels in Patients with Intractable Epilepsy.

The aim of the present study was to evaluate serum selenium levels in children receiving olive oil-based ketogenic diet (KD) for intractable seizures for at least 1year. Out of 320 patients who were initiated on KD, patients who continued receiving KD for at least 12months were enrolled. Sixteen patients who had selenium deficiency at the time of starting KD were excluded. Finally, a total of 110 patients (mean age 7.3±4.2years) were included. Serum selenium levels were measured at baseline and at 3, 6, and 12months after treatment initiation by using atomic absorption spectroscopy. Selenium deficiency was defined as a serum selenium level <48μg/L at each visit. Repeated measure ANOVA with post hoc Bonferroni correction was used for data analysis. Mean duration of KD was 15.3±4.3months. Mean serum selenium levels were significantly lower at 6 and 12months of KD treatment (66.2±23.3 and 57.2±16.2μg/L, respectively) compared to pre-treatment levels (79.3±25.7μg/L) (p=0.001). On the other hand, selenium levels did not show any significant difference at 3months of KD treatment (70.0±21.2μg/L) compared to baseline levels (p=0.076). A total of 54 patients (49.1%) were diagnosed with selenium deficiency, and oral selenium medication was initiated for these patients. No relevant clinical findings were detected, and echocardiographic findings were normal in all patients. The decline of the serum selenium concentrations after 6 and 12months of ketogenic diet suggests that patients on this highly prescriptive dietary treatment need close monitoring of this trace element.

Ketogenic diet effects on neurobehavioral development of children with intractable epilepsy: A prospective study.

This study aimed to determine the impact of a ketogenic diet (KD) on neurobehavioral development when used to treat children with intractable epilepsy, confirming the efficacy of the KD, as well as the correlation between early electroencephalography (EEG) changes in the early stage with treatment efficacy. We enrolled 42 children who were starting treatment for intractable epilepsy with the classic KD protocol. The total development quotient as well as the development quotients for adaptability, gross motor movements, fine motor movements, language, and individual-social interaction on the Gesell developmental scales were assessed before and after 3, 6, 12, and 18 months of KD treatment. The efficacy assessment was based on changes in seizure frequency after KD as recorded by the parents. We conducted 24-h video-EEG before and after 1 month of KD treatment. Developmental quotients of five energy regions in the Gesell developmental scales assessment were used to compare adaptability (P1=0.000), gross motor movements (P2=0.010), and fine motor movements (P3=0.000); the results showed significant differences. After KD treatment at different time points, 69.0%, 54.8%, 40.5%, and 33.3% patients, respectively, achieved a ≥50% reduction in seizure frequency. The reduction of epileptiform discharges in the awake state after 1 month of KD treatment correlated with the efficacy after 3 months of KD treatment. Ketogenic diet treatment tends to be associated with improved neurobehavioral development, and more significant improvement can be obtained with prolonged treatment. The KD is safe and effective in treating children with intractable epilepsy. Early EEG changes correlate with clinical efficacy, to a certain degree.

Can we predict efficacy of the ketogenic diet in children with refractory epilepsy?

The ketogenic diet (KD) can be effective in reducing seizures in children. Predictors of success have not been identified yet. To evaluate efficacy of KD treatment and to search for child- or diet-related factors that can predict its efficacy at 12 months follow-up. In addition we wish to determine the usefulness of a 3-month KD trial period. Single center retrospective study in a university paediatric hospital of children with refractory epilepsy in which the KD had been initiated. Patient and diet characteristics as well as seizure reduction data were obtained from medical records and parental review. Efficacy of the KD was defined as ≥ 50% seizure reduction. Variables were evaluated in their relation to a successful treatment at three and 12 months after diet initiation. During a 9.5-year period, the KD was initiated in 59 children with refractory epilepsy. Twenty-four children were still on the KD after 12 months, and 21 experienced ≥50% seizure reduction. Success of the KD at three months was significantly related to a successful response to KD treatment at 12 months (p<0.001). The KD can be an effective treatment in reducing seizures in children with refractory epilepsy. No significant relationships between variables and efficacy at 12 months were revealed. Children with a successful response at 3 months were significantly more likely to achieve success at 12 months of KD treatment.

Long-term impact of the ketogenic diet on growth and resting energy expenditure in children with intractable epilepsy.

The long-term effects of the ketogenic diet, a high fat diet for treating intractable epilepsy, on resting energy expenditure (REE) are unknown. The aim of this study was to evaluate the impact of 15 months of ketogenic diet treatment on growth and REE in children with intractable epilepsy. Growth, body composition, and REE were assessed at baseline, 3 months and 15 months in 24 children (14 males, 10 females; mean age 5 y 6 mo [SD 26 mo], range 7 mo-6 y 5 mo), 10 with cerebral palsy [CP]). Fifteen were identified as ketogenic diet responders at 3 months and continued on the ketogenic diet until 15 months. These were compared to 75 healthy children (43 males, 32 females; mean age 6 y 3 mo [SD 21 mo] age range 2-9 y). REE was expressed as percentage predicted, growth as height (HAz) and weight (WAz) z-scores, and body composition as fat and fat free mass (FFM). HAz declined -0.2 and -0.6 from baseline to 3 months and 15 months respectively (p = 0.001), while WAz was unchanged. In ketogenic diet responders, FFM, age and CP diagnosis predicted REE (overall R(2) = 0.76, p<0.001) and REE did not change. REE adjusted for FFM was lower (p<0.01) in children with CP at baseline (mean [standard error], -143[51] kcals/d) and 15 months (-198[53] kcals/d) compared to the healthy children. After 15 months of the ketogenic diet, linear growth status declined while weight status and REE were unchanged. REE remained reduced in children with CP.

Influence of ketogenic diet on the clinical effects and electroencephalogram features in 31 children with pharmacoresistant epileptic encephalopathy

To investigate the effect of ketogenic diet (KD) on the clinical and electroencephalogram features in children with pharmacoresistant epileptic encephalopathy. Thirty-one children (19 boys, 12 girls) aged 7 months to 7 years (mean 2 years 5 month) with epilepsy refractory to conventional antiepileptic drugs (AEDs) were included in this study. In addition to their original AED treatment, the children were assigned to different ketogenic diets based on their age. The prospective electro-clinical assessment was performed prior to the KD and then one week, one month and again 3 months after the initiation of therapy, respectively. The reduction of seizure frequency in 52%, 68% and 71% of all patients exceeded 50% one week, one month and three months after KD treatment respectively. KD is particularly effective in myoclonic astatic epilepsy (MAE; Doose Syndrome) and West syndrome with 100% and 81.25% of the patients having a greater than 50% seizure reduction, respectively. After 3 months of KD treatment, more than 2/3 patients experienced a reduction in interictal epileptiform discharges (IEDs) and improvement in EEG background. The clinical and electroencephalographic improvement confirms that KD is beneficial in children with refractory epilepsy.

The effect of the classical and medium chain triglyceride ketogenic diet on vitamin and mineral levels

The risk of nutritional deficiency in children on restrictive dietary treatments and a lack of ketogenic diet (KD)-specific UK supplements raises concerns about micronutrient status. Vitamin A, E, zinc, selenium and magnesium levels were therefore examined in children with intractable epilepsy treated with the KD. Plasma vitamins A and E, zinc, selenium and magnesium levels were measured at baseline and after 3, 6 and 12months on the classical (n=46) or medium chain triglyceride (MCT) (n=45) KD in children aged 2-16years, as part of a randomised trial, and pairwise comparisons with baseline were performed. Data were available from 91 children. From baseline to 12months, mean plasma vitamin A decreased from 1.41μmol L(-1) to 1.13μmol L(-1) in the classical group (P<0.001) but increased from 1.52μmol L(-1) to 1.81μmol L(-1) in the MCT group (P<0.001). Mean plasma vitamin E increased from 22.7μmol L(-1) to 33.2μmol L(-1) in the classical group (P<0.001) and from 22.3 μmol L(-1) to 23.3μmol L(-1) in the MCT group (P<0.05). No significant change in plasma zinc was seen at 12months, although mean plasma selenium decreased from 0.95μmol L(-1) to 0.88μmol L(-1) in the group as a whole (P<0.05). Mean plasma magnesium decreased from 0.87mmol L(-1) to 0.83mmol L(-1) in the group as a whole (P<0.001); when subdivided by KD type, this was limited to the classical group. Changes in plasma vitamins A and E and the decline in magnesium status after 12months of KD treatment suggest that micronutrient status may be suboptimal in this group and that available formulations for KD supplementation may need reviewing.

Manipulation of Types of Fats and Cholesterol Intake Can Successfully Improve the Lipid Profile While Maintaining the Efficacy of the Ketogenic Diet

The ketogenic diet (KD) is a dietary therapy that effectively treats intractable epilepsy in children. Hyperlipidemias are common side effects of KD and have been reported in approximately 30% to 50% of patients on this diet. Fats comprise 90% of the calories, and saturated fats are often used as 50% of the fat intake. The purpose of this study was to investigate whether alterations of the dietary fat sources can improve the lipid profiles while maintaining seizure control in the ketogenic diet. Using a retrospective chart review, the authors evaluated their practices of treating hyperlipidemias in 6 children on the KD who developed elevated lipid profiles. All had normal or mildly elevated lipid profiles before beginning the KD. The elevated lipid levels were detected after an average of 7 months of KD treatment. Changing the dietary fat types to mainly oils (polyunsaturated fats) and decreasing the use of protein foods high in saturated fats and cholesterol resulted in a normalized or baseline lipid profile in all 3 months later. Seizure control was unaffected. Hyperlipidemia is not a cause for discontinuing the KD and can be managed by changing the dietary fat sources.

Effects of ketogenic diet on epileptiform activity in children with therapy resistant epilepsy

The purpose was to quantify changes of epileptiform activity during ketogenic diet (KD) treatment in children with therapy resistant epilepsy, and evaluate how these changes are related to activity stage and to clinical effects on seizure frequency, seizure severity, attentional behaviour, quality of life (QOL), and beta-hydroxybutyrate (betaOHb). Eighteen children were investigated with 24h ambulatory EEG monitoring 1 week prior to KD initiation and, after 3 months of KD treatment. Epileptiform activity was evaluated by automated spike detection. This data was compared with data presented in a previous study published in Epilepsia 2006, on sleep structure and different activity stages, clinical data on seizure frequency, seizure severity, QOL and attentional behaviour on the same children [Hallbook, T., Lundgren, J., Rosén, I., 2007. Ketogenic diet improves sleep quality in children with therapy resistant epilepsy. Epilepsia 48, 59-65]. After 3 months of KD treatment the number of interictal epileptiform discharges (IEDs) was significantly reduced (p<0.001). When considering the four activity stages separately, the reduction was significant during non-rapid eye movement sleep stage 2, slow wave sleep (SWS) and rapid eye movement (REM) sleep (p=0.001, 0.001, 0.002), and not significantly so during awake (p=0.07). Beta-hydroxybutyrate was significantly increased (p<0.001). There was a significant correlation between the reduction in IEDs and clinical seizures (Spearman r=0.6, p=0.005) and between improvement in attentional behaviour and the increase in betaOHb (Spearman r=0.5, p=0.03). There was no significant correlation between changes in attentional behaviour and IEDs or clinical seizures. This study shows that KD reduces the number of IEDs, especially during sleep. It shows a correlation between reduction in epileptiform activity and clinical seizures. There were no correlations between reduction in epileptiform activity and clinical seizures and improvement in QOL or attention. The increase in betaOHb correlated with improvement in attention.

Ketogenic Diet Improves Sleep Quality in Children with Therapy‐resistant Epilepsy

The study purpose was to evaluate sleep structure during ketogenic diet (KD) treatment in children with therapy-resistant epilepsy and to correlate possible alterations with changes in clinical effects on seizure reduction, seizure severity, quality of life (QOL), and behavior. Eighteen children were examined with ambulatory polysomnographic recordings initially and after 3 months of KD treatment. Eleven children continued with the KD and were also evaluated after 12 months. Sleep parameters were estimated. Seizure frequency was recorded in a diary and seizure severity in the National Health Seizure Severity Scale (NHS3). QOL was assessed with a visual analogue scale. Child behavior checklist and Ponsford and Kinsella's rating scale of attentional behavior were used. KD induced a significant decrease in total sleep (p = 0.05) and total night sleep (p = 0.006). Slow wave sleep was preserved, rapid eye movement (REM) sleep increased (p = 0.01), sleep stage 2 decreased (p = 0.004), and sleep stage 1 was unchanged. Eleven children continued with the KD and were also evaluated after 12 months. They showed a significant decrease in daytime sleep (p = 0.01) and a further increase in REM sleep (p = 0.06). Seizure frequency (p = 0.001, p = 0.003), seizure severity (p < 0.001, p = 0.005) and QOL (p < 0.001, p = 0.005) were significantly improved at 3 and 12 months. Attentional behavior was also improved, significantly so at 3 months (p = 0.003). There was a significant correlation between increased REM sleep and improvement in QOL (Spearman r = 0.6, p = 0.01) at 3 months. KD decreases sleep and improves sleep quality in children with therapy-resistant epilepsy. The improvement in sleep quality, with increased REM sleep, seems to contribute to the improvement in QOL.